Immune complexes and the complement factors C4 and C3 in cerebrospinal fluid and serum from patients with chronic progressive multiple sclerosis

Abstract

Immune complexes (IC) have been found in both serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS). The complement system is known to play a major role as a mediator of inflammation in immune complex disease. Therefore, we have investigated paired samples of serum and CSF from 32 patients with progressive MS for IC, the levels of the complement factors C4 and C3, and presence of their activation products (AP). IC was found in serum from 17 of the 32 MS patients (53%) and in CSF from 9 of 31 MS patients (29%). No correlation was found between the occurrence of IC in serum and in CSF. The levels of C3 in serum and CSF from the MS patients did not differ from the levels in a control group, whereas the levels of C4 in MS-serum were elevated and the C4 levels in MS-CSF reduced. A low level of CSF-C4 correlated significantly to the occurrence of CSF-IC. AP of C4 and C3 in serum were seen in 11 of the 32 patients (34%), appearing significantly more frequently among patients with circulating IC. No C4- or C3AP could be identified in CSF.

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system

“…With respect to MS patients C3 and C4 concentrations (expressed as a percentage of the total CSF protein) were signi®cantly increased during exacerbations (11), and normal in unselected patients (12). In SP patients CSF and serum C3 levels did not differ from controls, whereas CSF and serum C4 concentrations were reduced and elevated, respectively (13). We found that in both RR and SP patients without exacerbations mean C3 index was increased and mean CSF C3 level was decreased, whereas corresponding C4 values were normal.…”

Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease

“…Direct evidence of oligodendrocyte injury in early lesions, rather than death, has been presented [ 184], with indirect findings based on spinal fluid analysis implicating complement as a cause of reversible oligodendrocyte injury in multiple sclerosis [ 197]. Complement activation in multiple sclerosis has been long suggested on the basis of decreased native components, and increased activation products, in spinal fluid samples [ 88, 134, 188] and deposits of C9 and complement membrane attack complex within lesions have also been found [ 36]. More recently, C9‐neoantigen deposits were demonstrated in areas of active myelin destruction, accompanied by loss of oligodendrocytes, albeit incomplete [ 218], while membrane receptors for the anaphylotoxins C3a and C5a are abundantly expressed in distributions, respectively, peri‐vascular [ 63] or on foamy macrophages or astrocytes [ 137].…”

Complement Protein Isoforms in CSF as Possible Biomarkers for Neurodegenerative Disease

“…Previous studies have investigated complement proteins in cerebrospinal fluid (CSF) as possible biomarkers of central nervous system disease [8,[10][11][12][13][14]. In these studies, the concentration of complement components or factors was measured using antibody-based techniques such as ELISA or other immunoassays.…”

“…In these studies, the concentration of complement components or factors was measured using antibody-based techniques such as ELISA or other immunoassays. The results of these studies suggest that the CSF concentrations of complement proteins C3, C4, and the C5b-9 complex can differentiate between normal subjects and patients with MS [10][11][12]. For AD, previous studies have found inconclusive results when comparing the total amount of C3a [15] and mixed results comparing total amount of C1q [14,16] in the CSF between AD patients and controls.…”